CA2712914C - Derives bicycliques de carboxamides azabicycliques, leur preparation et leur application en therapeutique - Google Patents

Derives bicycliques de carboxamides azabicycliques, leur preparation et leur application en therapeutique Download PDF

Info

Publication number: CA2712914C
Authority: CA; Canada
Prior art keywords: methyl; pyridin; indole; carboxamide; group
Prior art date: 2008-01-22
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Expired - Fee Related

Application number

CA2712914A

Other languages

English (en)

French (fr)

Other versions

CA2712914A1 (fr

Inventor

Laurent Dubois

Yannick Evanno

Catherine Gille

Andre Malanda

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Sanofi Aventis France

Original Assignee

Sanofi Aventis France

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

2008-01-22

Filing date

2009-01-20

Publication date

2016-08-16

2009-01-20 Application filed by Sanofi Aventis France filed Critical Sanofi Aventis France

2009-09-17 Publication of CA2712914A1 publication Critical patent/CA2712914A1/fr

2016-08-16 Application granted granted Critical

2016-08-16 Publication of CA2712914C publication Critical patent/CA2712914C/fr

Status Expired - Fee Related legal-status Critical Current

2029-01-20 Anticipated expiration legal-status Critical

Links

238000002360 preparation method Methods 0.000 title claims description 15
125000002619 bicyclic group Chemical group 0.000 title description 4
230000001225 therapeutic effect Effects 0.000 title description 4
150000003857 carboxamides Chemical class 0.000 title description 3
150000001875 compounds Chemical class 0.000 claims description 309
-1 C1-C6-alkyl Chemical group 0.000 claims description 113
238000000034 method Methods 0.000 claims description 71
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 62
229910052757 nitrogen Inorganic materials 0.000 claims description 46
230000008569 process Effects 0.000 claims description 45
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 44
125000004429 atom Chemical group 0.000 claims description 43
238000006243 chemical reaction Methods 0.000 claims description 43
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 42
150000003839 salts Chemical class 0.000 claims description 39
239000002253 acid Substances 0.000 claims description 37
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 34
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 31
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 30
229910052799 carbon Inorganic materials 0.000 claims description 25
125000004433 nitrogen atom Chemical group N* 0.000 claims description 25
239000002904 solvent Substances 0.000 claims description 25
125000002733 (C1-C6) fluoroalkyl group Chemical group 0.000 claims description 24
125000005843 halogen group Chemical group 0.000 claims description 24
229910052739 hydrogen Inorganic materials 0.000 claims description 18
239000001257 hydrogen Substances 0.000 claims description 18
229910052701 rubidium Inorganic materials 0.000 claims description 14
125000004432 carbon atom Chemical group C* 0.000 claims description 13
229910052717 sulfur Inorganic materials 0.000 claims description 12
125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 11
125000004430 oxygen atom Chemical group O* 0.000 claims description 11
XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 claims description 10
125000004093 cyano group Chemical group *C#N 0.000 claims description 10
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 10
JLTRXTDYQLMHGR-UHFFFAOYSA-N trimethylaluminium Chemical compound C[Al](C)C JLTRXTDYQLMHGR-UHFFFAOYSA-N 0.000 claims description 9
229910052727 yttrium Inorganic materials 0.000 claims description 9
208000002193 Pain Diseases 0.000 claims description 8
150000001408 amides Chemical class 0.000 claims description 8
239000003153 chemical reaction reagent Substances 0.000 claims description 8
239000003814 drug Substances 0.000 claims description 8
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 8
230000036407 pain Effects 0.000 claims description 8
239000000460 chlorine Substances 0.000 claims description 7
229910052801 chlorine Inorganic materials 0.000 claims description 7
238000011282 treatment Methods 0.000 claims description 7
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 6
208000035475 disorder Diseases 0.000 claims description 6
125000004076 pyridyl group Chemical group 0.000 claims description 6
125000000437 thiazol-2-yl group Chemical group [H]C1=C([H])N=C(*)S1 0.000 claims description 6
150000003573 thiols Chemical class 0.000 claims description 6
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 5
108010025083 TRPV1 receptor Proteins 0.000 claims description 5
150000001412 amines Chemical class 0.000 claims description 5
125000003277 amino group Chemical group 0.000 claims description 5
230000003197 catalytic effect Effects 0.000 claims description 5
239000000546 pharmaceutical excipient Substances 0.000 claims description 5
229910000073 phosphorus hydride Inorganic materials 0.000 claims description 5
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 5
125000000335 thiazolyl group Chemical group 0.000 claims description 5
229910052721 tungsten Inorganic materials 0.000 claims description 5
125000003545 alkoxy group Chemical group 0.000 claims description 4
201000010099 disease Diseases 0.000 claims description 4
229910052736 halogen Inorganic materials 0.000 claims description 4
150000002367 halogens Chemical group 0.000 claims description 4
125000000842 isoxazolyl group Chemical group 0.000 claims description 4
239000008194 pharmaceutical composition Substances 0.000 claims description 4
125000002098 pyridazinyl group Chemical group 0.000 claims description 4
125000000714 pyrimidinyl group Chemical group 0.000 claims description 4
238000010992 reflux Methods 0.000 claims description 4
125000004434 sulfur atom Chemical group 0.000 claims description 4
125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 3
XJBPQCXJJGPBHN-UHFFFAOYSA-N 5-fluoro-1-[(3-fluorophenyl)methyl]-n-(3-methylimidazo[4,5-b]pyridin-6-yl)indole-2-carboxamide Chemical compound C=1N=C2N(C)C=NC2=CC=1NC(=O)C1=CC2=CC(F)=CC=C2N1CC1=CC=CC(F)=C1 XJBPQCXJJGPBHN-UHFFFAOYSA-N 0.000 claims description 3
HTXZSJXJVVQTMW-UHFFFAOYSA-N 5-fluoro-1-[(3-fluorophenyl)methyl]-n-(4-methyl-2,3-dihydropyrido[3,2-b][1,4]oxazin-7-yl)indole-2-carboxamide Chemical compound C=1N=C2N(C)CCOC2=CC=1NC(=O)C1=CC2=CC(F)=CC=C2N1CC1=CC=CC(F)=C1 HTXZSJXJVVQTMW-UHFFFAOYSA-N 0.000 claims description 3
206010028980 Neoplasm Diseases 0.000 claims description 3
150000001879 copper Chemical class 0.000 claims description 3
239000007822 coupling agent Substances 0.000 claims description 3
125000002541 furyl group Chemical group 0.000 claims description 3
125000002883 imidazolyl group Chemical group 0.000 claims description 3
125000001786 isothiazolyl group Chemical group 0.000 claims description 3
239000003446 ligand Substances 0.000 claims description 3
JOWXKNYJROAERR-UHFFFAOYSA-N n-[2-(hydroxymethyl)-[1,3]thiazolo[5,4-b]pyridin-6-yl]-1-(1,3-thiazol-2-ylmethyl)-5-(trifluoromethyl)indole-2-carboxamide Chemical compound C=1N=C2SC(CO)=NC2=CC=1NC(=O)C1=CC2=CC(C(F)(F)F)=CC=C2N1CC1=NC=CS1 JOWXKNYJROAERR-UHFFFAOYSA-N 0.000 claims description 3
CXBUZJQXFQSSHA-UHFFFAOYSA-N n-[2-(hydroxymethyl)-[1,3]thiazolo[5,4-b]pyridin-6-yl]-1-[(3-methylphenyl)methyl]-5-(trifluoromethyl)indole-2-carboxamide Chemical compound CC1=CC=CC(CN2C3=CC=C(C=C3C=C2C(=O)NC=2C=C3N=C(CO)SC3=NC=2)C(F)(F)F)=C1 CXBUZJQXFQSSHA-UHFFFAOYSA-N 0.000 claims description 3
125000001715 oxadiazolyl group Chemical group 0.000 claims description 3
125000002971 oxazolyl group Chemical group 0.000 claims description 3
239000002798 polar solvent Substances 0.000 claims description 3
230000002265 prevention Effects 0.000 claims description 3
125000003373 pyrazinyl group Chemical group 0.000 claims description 3
125000003226 pyrazolyl group Chemical group 0.000 claims description 3
125000003831 tetrazolyl group Chemical group 0.000 claims description 3
125000001113 thiadiazolyl group Chemical group 0.000 claims description 3
125000001544 thienyl group Chemical group 0.000 claims description 3
125000004306 triazinyl group Chemical group 0.000 claims description 3
125000001425 triazolyl group Chemical group 0.000 claims description 3
RKTAUAMJQPASHC-UHFFFAOYSA-N 5-fluoro-1-[(3-fluorophenyl)methyl]-n-(1-methyl-2-oxopyrido[2,3-b][1,4]oxazin-7-yl)indole-2-carboxamide Chemical compound C1=C2N(C)C(=O)COC2=NC=C1NC(=O)C1=CC2=CC(F)=CC=C2N1CC1=CC=CC(F)=C1 RKTAUAMJQPASHC-UHFFFAOYSA-N 0.000 claims description 2
OPFQTBNXOJXHHP-UHFFFAOYSA-N 5-fluoro-1-[(3-fluorophenyl)methyl]-n-(2-methyl-1h-imidazo[4,5-b]pyridin-6-yl)indole-2-carboxamide Chemical compound C=1N=C2NC(C)=NC2=CC=1NC(=O)C1=CC2=CC(F)=CC=C2N1CC1=CC=CC(F)=C1 OPFQTBNXOJXHHP-UHFFFAOYSA-N 0.000 claims description 2
DLLBPQJYPQYIHM-UHFFFAOYSA-N 5-fluoro-1-[(3-fluorophenyl)methyl]-n-(2-methyl-[1,3]thiazolo[5,4-b]pyridin-6-yl)indole-2-carboxamide Chemical compound C=1N=C2SC(C)=NC2=CC=1NC(=O)C1=CC2=CC(F)=CC=C2N1CC1=CC=CC(F)=C1 DLLBPQJYPQYIHM-UHFFFAOYSA-N 0.000 claims description 2
BZPKSAWBKDCAHO-UHFFFAOYSA-N 5-fluoro-1-[(3-fluorophenyl)methyl]-n-(6-hydroxy-5,6,7,8-tetrahydroquinolin-3-yl)indole-2-carboxamide Chemical compound C1=C2CC(O)CCC2=NC=C1NC(=O)C1=CC2=CC(F)=CC=C2N1CC1=CC=CC(F)=C1 BZPKSAWBKDCAHO-UHFFFAOYSA-N 0.000 claims description 2
MXJOYEZFRBOWPU-UHFFFAOYSA-N 5-fluoro-1-[(3-fluorophenyl)methyl]-n-([1,3]thiazolo[5,4-b]pyridin-6-yl)indole-2-carboxamide Chemical compound FC1=CC=CC(CN2C3=CC=C(F)C=C3C=C2C(=O)NC=2C=C3N=CSC3=NC=2)=C1 MXJOYEZFRBOWPU-UHFFFAOYSA-N 0.000 claims description 2
HGGLSFHQCIEBBQ-UHFFFAOYSA-N 5-fluoro-1-[(3-fluorophenyl)methyl]-n-[2-(hydroxymethyl)-3-methylimidazo[4,5-b]pyridin-6-yl]indole-2-carboxamide Chemical compound C=1N=C2N(C)C(CO)=NC2=CC=1NC(=O)C1=CC2=CC(F)=CC=C2N1CC1=CC=CC(F)=C1 HGGLSFHQCIEBBQ-UHFFFAOYSA-N 0.000 claims description 2
IEBKVHYVEZSRDQ-UHFFFAOYSA-N 5-fluoro-1-[(3-fluorophenyl)methyl]-n-[2-(hydroxymethyl)-[1,3]thiazolo[5,4-b]pyridin-6-yl]indole-2-carboxamide Chemical compound C=1N=C2SC(CO)=NC2=CC=1NC(=O)C1=CC2=CC(F)=CC=C2N1CC1=CC=CC(F)=C1 IEBKVHYVEZSRDQ-UHFFFAOYSA-N 0.000 claims description 2
RGQLKMLLHMJZRM-UHFFFAOYSA-N 5-fluoro-1-[(3-fluorophenyl)methyl]-n-quinolin-3-ylindole-2-carboxamide Chemical compound FC1=CC=CC(CN2C3=CC=C(F)C=C3C=C2C(=O)NC=2C=C3C=CC=CC3=NC=2)=C1 RGQLKMLLHMJZRM-UHFFFAOYSA-N 0.000 claims description 2
RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims description 2
208000018522 Gastrointestinal disease Diseases 0.000 claims description 2
XQFRJNBWHJMXHO-RRKCRQDMSA-N IDUR Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 XQFRJNBWHJMXHO-RRKCRQDMSA-N 0.000 claims description 2
206010061218 Inflammation Diseases 0.000 claims description 2
208000003251 Pruritus Diseases 0.000 claims description 2
201000004681 Psoriasis Diseases 0.000 claims description 2
230000009471 action Effects 0.000 claims description 2
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 2
229910052802 copper Inorganic materials 0.000 claims description 2
239000010949 copper Substances 0.000 claims description 2
230000004054 inflammatory process Effects 0.000 claims description 2
208000030159 metabolic disease Diseases 0.000 claims description 2
210000004400 mucous membrane Anatomy 0.000 claims description 2
201000006417 multiple sclerosis Diseases 0.000 claims description 2
HYUVOZYIDIRKDX-UHFFFAOYSA-N n-(2,3-dimethylimidazo[4,5-b]pyridin-6-yl)-1-[(3-fluorophenyl)methyl]-5-(trifluoromethyl)pyrrolo[2,3-b]pyridine-2-carboxamide Chemical compound C=1N=C2N(C)C(C)=NC2=CC=1NC(=O)C1=CC2=CC(C(F)(F)F)=CN=C2N1CC1=CC=CC(F)=C1 HYUVOZYIDIRKDX-UHFFFAOYSA-N 0.000 claims description 2
PRTCOZOHXOTUEA-UHFFFAOYSA-N n-(2,3-dimethylimidazo[4,5-b]pyridin-6-yl)-5-fluoro-1-[(3-fluorophenyl)methyl]indole-2-carboxamide Chemical compound C=1N=C2N(C)C(C)=NC2=CC=1NC(=O)C1=CC2=CC(F)=CC=C2N1CC1=CC=CC(F)=C1 PRTCOZOHXOTUEA-UHFFFAOYSA-N 0.000 claims description 2
NCAQULMICWGYER-UHFFFAOYSA-N n-[2-(hydroxymethyl)-[1,3]thiazolo[5,4-b]pyridin-6-yl]-1-(1,3-thiazol-2-ylmethyl)-5-trimethylsilylindole-2-carboxamide Chemical compound C=1N=C2SC(CO)=NC2=CC=1NC(=O)C1=CC2=CC([Si](C)(C)C)=CC=C2N1CC1=NC=CS1 NCAQULMICWGYER-UHFFFAOYSA-N 0.000 claims description 2
ASNDFFDQCFOBDN-UHFFFAOYSA-N n-[2-(hydroxymethyl)-[1,3]thiazolo[5,4-b]pyridin-6-yl]-1-(1,3-thiazol-2-ylmethyl)-6-(trifluoromethyl)indole-2-carboxamide Chemical compound C=1N=C2SC(CO)=NC2=CC=1NC(=O)C1=CC2=CC=C(C(F)(F)F)C=C2N1CC1=NC=CS1 ASNDFFDQCFOBDN-UHFFFAOYSA-N 0.000 claims description 2
YDMSZUAZQWKXSM-UHFFFAOYSA-N n-[2-(hydroxymethyl)-[1,3]thiazolo[5,4-b]pyridin-6-yl]-1-(pyridin-4-ylmethyl)-5-(trifluoromethyl)indole-2-carboxamide Chemical compound C=1N=C2SC(CO)=NC2=CC=1NC(=O)C1=CC2=CC(C(F)(F)F)=CC=C2N1CC1=CC=NC=C1 YDMSZUAZQWKXSM-UHFFFAOYSA-N 0.000 claims description 2
XIFKXKOHQHQJFH-UHFFFAOYSA-N n-[2-(hydroxymethyl)-[1,3]thiazolo[5,4-b]pyridin-6-yl]-1-(pyridin-4-ylmethyl)-6-trimethylsilylindole-2-carboxamide Chemical compound C12=CC([Si](C)(C)C)=CC=C2C=C(C(=O)NC=2C=C3N=C(CO)SC3=NC=2)N1CC1=CC=NC=C1 XIFKXKOHQHQJFH-UHFFFAOYSA-N 0.000 claims description 2
JECIYXDXVXDKST-UHFFFAOYSA-N n-[2-(hydroxymethyl)-[1,3]thiazolo[5,4-b]pyridin-6-yl]-1-[(3-methylphenyl)methyl]-5-(trifluoromethyl)pyrrolo[2,3-b]pyridine-2-carboxamide Chemical compound CC1=CC=CC(CN2C3=NC=C(C=C3C=C2C(=O)NC=2C=C3N=C(CO)SC3=NC=2)C(F)(F)F)=C1 JECIYXDXVXDKST-UHFFFAOYSA-N 0.000 claims description 2
OSQAGWCCRJOWPT-UHFFFAOYSA-N n-[2-(hydroxymethyl)-[1,3]thiazolo[5,4-b]pyridin-6-yl]-1-[(3-methylphenyl)methyl]-5-trimethylsilylindole-2-carboxamide Chemical compound CC1=CC=CC(CN2C3=CC=C(C=C3C=C2C(=O)NC=2C=C3N=C(CO)SC3=NC=2)[Si](C)(C)C)=C1 OSQAGWCCRJOWPT-UHFFFAOYSA-N 0.000 claims description 2
ZXTAHSRUDKPAFQ-UHFFFAOYSA-N n-[2-(hydroxymethyl)-[1,3]thiazolo[5,4-b]pyridin-6-yl]-1-[(3-methylphenyl)methyl]-6-trimethylsilylindole-2-carboxamide Chemical compound CC1=CC=CC(CN2C3=CC(=CC=C3C=C2C(=O)NC=2C=C3N=C(CO)SC3=NC=2)[Si](C)(C)C)=C1 ZXTAHSRUDKPAFQ-UHFFFAOYSA-N 0.000 claims description 2
VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 claims description 2
239000011347 resin Substances 0.000 claims description 2
229920005989 resin Polymers 0.000 claims description 2
230000000241 respiratory effect Effects 0.000 claims description 2
230000036556 skin irritation Effects 0.000 claims description 2
DBPUJFIQWFGKTD-UHFFFAOYSA-N 6-fluoro-n-[2-(hydroxymethyl)-[1,3]thiazolo[5,4-b]pyridin-6-yl]-1-(pyridin-4-ylmethyl)indole-2-carboxamide Chemical compound C=1N=C2SC(CO)=NC2=CC=1NC(=O)C1=CC2=CC=C(F)C=C2N1CC1=CC=NC=C1 DBPUJFIQWFGKTD-UHFFFAOYSA-N 0.000 claims 1
HYKYEDXMEJHDLQ-UHFFFAOYSA-N 6-fluoro-n-[2-(hydroxymethyl)-[1,3]thiazolo[5,4-b]pyridin-6-yl]-1-[(3-methylphenyl)methyl]indole-2-carboxamide Chemical compound CC1=CC=CC(CN2C3=CC(F)=CC=C3C=C2C(=O)NC=2C=C3N=C(CO)SC3=NC=2)=C1 HYKYEDXMEJHDLQ-UHFFFAOYSA-N 0.000 claims 1
FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 claims 1
FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 claims 1
238000004519 manufacturing process Methods 0.000 claims 1
ZCKDOCZOFAIWPV-UHFFFAOYSA-N n-(3,4-dihydro-2h-pyrido[3,2-b][1,4]oxazin-7-yl)-5-fluoro-1-[(3-fluorophenyl)methyl]indole-2-carboxamide Chemical compound FC1=CC=CC(CN2C3=CC=C(F)C=C3C=C2C(=O)NC=2C=C3OCCNC3=NC=2)=C1 ZCKDOCZOFAIWPV-UHFFFAOYSA-N 0.000 claims 1
GAZXYOMJNUOAGV-UHFFFAOYSA-N n-[2-(hydroxymethyl)-[1,3]thiazolo[5,4-b]pyridin-6-yl]-1-(1,3-thiazol-2-ylmethyl)-5-(trifluoromethyl)pyrrolo[2,3-b]pyridine-2-carboxamide Chemical compound C=1N=C2SC(CO)=NC2=CC=1NC(=O)C1=CC2=CC(C(F)(F)F)=CN=C2N1CC1=NC=CS1 GAZXYOMJNUOAGV-UHFFFAOYSA-N 0.000 claims 1
DILDASOODDKWQW-UHFFFAOYSA-N n-[2-(hydroxymethyl)-[1,3]thiazolo[5,4-b]pyridin-6-yl]-1-(pyridin-4-ylmethyl)-5-(trifluoromethyl)pyrrolo[2,3-b]pyridine-2-carboxamide Chemical compound C=1N=C2SC(CO)=NC2=CC=1NC(=O)C1=CC2=CC(C(F)(F)F)=CN=C2N1CC1=CC=NC=C1 DILDASOODDKWQW-UHFFFAOYSA-N 0.000 claims 1
SXLNZVRMDIUBPW-UHFFFAOYSA-N n-[2-(hydroxymethyl)-[1,3]thiazolo[5,4-b]pyridin-6-yl]-1-(pyridin-4-ylmethyl)-6-(trifluoromethyl)indole-2-carboxamide Chemical compound C=1N=C2SC(CO)=NC2=CC=1NC(=O)C1=CC2=CC=C(C(F)(F)F)C=C2N1CC1=CC=NC=C1 SXLNZVRMDIUBPW-UHFFFAOYSA-N 0.000 claims 1
IEOOBSOXZJIRIY-UHFFFAOYSA-N n-[2-(hydroxymethyl)-[1,3]thiazolo[5,4-b]pyridin-6-yl]-1-[(3-methylphenyl)methyl]-6-(trifluoromethyl)indole-2-carboxamide Chemical compound CC1=CC=CC(CN2C3=CC(=CC=C3C=C2C(=O)NC=2C=C3N=C(CO)SC3=NC=2)C(F)(F)F)=C1 IEOOBSOXZJIRIY-UHFFFAOYSA-N 0.000 claims 1
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 77
239000000047 product Substances 0.000 description 72
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 70
238000005160 1H NMR spectroscopy Methods 0.000 description 65
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 60
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 60
239000000243 solution Substances 0.000 description 51
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 42
239000000203 mixture Substances 0.000 description 42
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 40
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 39
238000007792 addition Methods 0.000 description 33
125000003118 aryl group Chemical group 0.000 description 33
YKPUWZUDDOIDPM-SOFGYWHQSA-N capsaicin Chemical compound COC1=CC(CNC(=O)CCCC\C=C\C(C)C)=CC=C1O YKPUWZUDDOIDPM-SOFGYWHQSA-N 0.000 description 32
239000002585 base Substances 0.000 description 24
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 23
XISIVGAOCAACKR-UHFFFAOYSA-H 2,2,3,3,4,4,4-heptafluorobutanoate;rhodium(3+) Chemical class [Rh+3].[Rh+3].[O-]C(=O)C(F)(F)C(F)(F)C(F)(F)F.[O-]C(=O)C(F)(F)C(F)(F)C(F)(F)F.[O-]C(=O)C(F)(F)C(F)(F)C(F)(F)F.[O-]C(=O)C(F)(F)C(F)(F)C(F)(F)F.[O-]C(=O)C(F)(F)C(F)(F)C(F)(F)F.[O-]C(=O)C(F)(F)C(F)(F)C(F)(F)F XISIVGAOCAACKR-UHFFFAOYSA-H 0.000 description 22
239000011541 reaction mixture Substances 0.000 description 22
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 20
125000001072 heteroaryl group Chemical group 0.000 description 20
238000004895 liquid chromatography mass spectrometry Methods 0.000 description 19
125000004191 (C1-C6) alkoxy group Chemical group 0.000 description 17
150000001721 carbon Chemical group 0.000 description 17
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 16
239000000377 silicon dioxide Substances 0.000 description 16
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
229960002504 capsaicin Drugs 0.000 description 15
235000017663 capsaicin Nutrition 0.000 description 15
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 15
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 14
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
238000003756 stirring Methods 0.000 description 14
125000000623 heterocyclic group Chemical group 0.000 description 13
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
238000004587 chromatography analysis Methods 0.000 description 12
239000012074 organic phase Substances 0.000 description 12
229920006395 saturated elastomer Polymers 0.000 description 12
239000007787 solid Substances 0.000 description 12
125000001424 substituent group Chemical group 0.000 description 12
210000004027 cell Anatomy 0.000 description 11
125000000753 cycloalkyl group Chemical group 0.000 description 11
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 10
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 10
125000000217 alkyl group Chemical group 0.000 description 10
238000001914 filtration Methods 0.000 description 10
229910052731 fluorine Inorganic materials 0.000 description 10
239000011734 sodium Substances 0.000 description 10
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 9
239000012298 atmosphere Substances 0.000 description 9
230000015572 biosynthetic process Effects 0.000 description 9
230000005764 inhibitory process Effects 0.000 description 9
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
OZMLUMPWPFZWTP-UHFFFAOYSA-N 2-(tributyl-$l^{5}-phosphanylidene)acetonitrile Chemical compound CCCCP(CCCC)(CCCC)=CC#N OZMLUMPWPFZWTP-UHFFFAOYSA-N 0.000 description 8
MPNDQLDEDAQJDE-UHFFFAOYSA-N 5-fluoro-1-[(3-fluorophenyl)methyl]indole-2-carboxylic acid Chemical compound OC(=O)C1=CC2=CC(F)=CC=C2N1CC1=CC=CC(F)=C1 MPNDQLDEDAQJDE-UHFFFAOYSA-N 0.000 description 8
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 8
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 8
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 8
125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 description 8
239000000741 silica gel Substances 0.000 description 8
229910002027 silica gel Inorganic materials 0.000 description 8
229910052708 sodium Inorganic materials 0.000 description 8
229910052938 sodium sulfate Inorganic materials 0.000 description 8
235000011152 sodium sulphate Nutrition 0.000 description 8
238000003786 synthesis reaction Methods 0.000 description 8
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 7
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 7
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 7
230000006978 adaptation Effects 0.000 description 7
238000003818 flash chromatography Methods 0.000 description 7
239000003921 oil Substances 0.000 description 7
230000004044 response Effects 0.000 description 7
239000011780 sodium chloride Substances 0.000 description 7
239000000725 suspension Substances 0.000 description 7
102000003566 TRPV1 Human genes 0.000 description 6
101150016206 Trpv1 gene Proteins 0.000 description 6
125000001153 fluoro group Chemical group F* 0.000 description 6
239000000499 gel Substances 0.000 description 6
125000005842 heteroatom Chemical group 0.000 description 6
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
239000002244 precipitate Substances 0.000 description 6
210000003594 spinal ganglia Anatomy 0.000 description 6
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 5
239000008346 aqueous phase Substances 0.000 description 5
239000007864 aqueous solution Substances 0.000 description 5
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 5
229910052794 bromium Inorganic materials 0.000 description 5
239000000706 filtrate Substances 0.000 description 5
230000003040 nociceptive effect Effects 0.000 description 5
238000000746 purification Methods 0.000 description 5
239000012047 saturated solution Substances 0.000 description 5
239000012453 solvate Substances 0.000 description 5
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
SWYYKOLYMSRNQG-UHFFFAOYSA-N 3-methyl-6-nitroimidazo[4,5-b]pyridine Chemical compound [O-][N+](=O)C1=CN=C2N(C)C=NC2=C1 SWYYKOLYMSRNQG-UHFFFAOYSA-N 0.000 description 4
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 4
241000700159 Rattus Species 0.000 description 4
238000004440 column chromatography Methods 0.000 description 4
238000005859 coupling reaction Methods 0.000 description 4
238000001035 drying Methods 0.000 description 4
230000000694 effects Effects 0.000 description 4
239000011737 fluorine Substances 0.000 description 4
239000012299 nitrogen atmosphere Substances 0.000 description 4
125000002524 organometallic group Chemical group 0.000 description 4
229910052763 palladium Inorganic materials 0.000 description 4
230000007170 pathology Effects 0.000 description 4
239000000843 powder Substances 0.000 description 4
239000000126 substance Substances 0.000 description 4
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 4
JKHRBUOBGSPOLN-UHFFFAOYSA-N (3-methyl-6-nitroimidazo[4,5-b]pyridin-2-yl)methanol Chemical compound [O-][N+](=O)C1=CN=C2N(C)C(CO)=NC2=C1 JKHRBUOBGSPOLN-UHFFFAOYSA-N 0.000 description 3
125000006570 (C5-C6) heteroaryl group Chemical group 0.000 description 3
ZHAKAIBZKYHXJS-UHFFFAOYSA-N 2-(chloromethyl)-1,3-thiazole Chemical compound ClCC1=NC=CS1 ZHAKAIBZKYHXJS-UHFFFAOYSA-N 0.000 description 3
ZMYDAPJHGNEFGQ-UHFFFAOYSA-N 6-(2-fluorophenyl)-5h-[1,3]dioxolo[4,5-g]quinolin-8-one Chemical compound FC1=CC=CC=C1C(NC1=C2)=CC(=O)C1=CC1=C2OCO1 ZMYDAPJHGNEFGQ-UHFFFAOYSA-N 0.000 description 3
125000004939 6-pyridyl group Chemical group N1=CC=CC=C1* 0.000 description 3
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
241001465754 Metazoa Species 0.000 description 3
241000699666 Mus <mouse, genus> Species 0.000 description 3
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
150000007513 acids Chemical class 0.000 description 3
239000000556 agonist Substances 0.000 description 3
PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 3
235000019270 ammonium chloride Nutrition 0.000 description 3
239000005557 antagonist Substances 0.000 description 3
AEOCXXJPGCBFJA-UHFFFAOYSA-N ethionamide Chemical compound CCC1=CC(C(N)=S)=CC=N1 AEOCXXJPGCBFJA-UHFFFAOYSA-N 0.000 description 3
MXENQUDWAJFZBL-UHFFFAOYSA-N ethyl 5-trimethylsilyl-1h-indole-2-carboxylate Chemical compound C[Si](C)(C)C1=CC=C2NC(C(=O)OCC)=CC2=C1 MXENQUDWAJFZBL-UHFFFAOYSA-N 0.000 description 3
238000005755 formation reaction Methods 0.000 description 3
239000011521 glass Substances 0.000 description 3
GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 3
238000000338 in vitro Methods 0.000 description 3
238000001727 in vivo Methods 0.000 description 3
229910052751 metal Inorganic materials 0.000 description 3
239000002184 metal Substances 0.000 description 3
229910052700 potassium Inorganic materials 0.000 description 3
239000011591 potassium Substances 0.000 description 3
229910000027 potassium carbonate Inorganic materials 0.000 description 3
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
JXQZFRPARQBDKV-UHFFFAOYSA-N (3-bromophenyl)-trimethylsilane Chemical compound C[Si](C)(C)C1=CC=CC(Br)=C1 JXQZFRPARQBDKV-UHFFFAOYSA-N 0.000 description 2
XLDTZYAXUPGUMQ-UHFFFAOYSA-N (6-amino-3-methylimidazo[4,5-b]pyridin-2-yl)methanol Chemical compound NC1=CN=C2N(C)C(CO)=NC2=C1 XLDTZYAXUPGUMQ-UHFFFAOYSA-N 0.000 description 2
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 2
DFDSVWQRHNGXRZ-UHFFFAOYSA-N 2-methyl-1h-imidazo[4,5-b]pyridin-6-amine Chemical compound NC1=CN=C2NC(C)=NC2=C1 DFDSVWQRHNGXRZ-UHFFFAOYSA-N 0.000 description 2
ZNFLHCKSMCSEGW-UHFFFAOYSA-N 3-trimethylsilylbenzaldehyde Chemical compound C[Si](C)(C)C1=CC=CC(C=O)=C1 ZNFLHCKSMCSEGW-UHFFFAOYSA-N 0.000 description 2
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 2
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
241000699670 Mus sp. Species 0.000 description 2
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 2
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
239000004480 active ingredient Substances 0.000 description 2
125000002947 alkylene group Chemical group 0.000 description 2
230000003042 antagnostic effect Effects 0.000 description 2
125000004104 aryloxy group Chemical group 0.000 description 2
210000003050 axon Anatomy 0.000 description 2
125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 2
HTZCNXWZYVXIMZ-UHFFFAOYSA-M benzyl(triethyl)azanium;chloride Chemical compound [Cl-].CC[N+](CC)(CC)CC1=CC=CC=C1 HTZCNXWZYVXIMZ-UHFFFAOYSA-M 0.000 description 2
210000004556 brain Anatomy 0.000 description 2
239000007795 chemical reaction product Substances 0.000 description 2
239000003795 chemical substances by application Substances 0.000 description 2
125000001309 chloro group Chemical group Cl* 0.000 description 2
239000012230 colorless oil Substances 0.000 description 2
GBRBMTNGQBKBQE-UHFFFAOYSA-L copper;diiodide Chemical compound I[Cu]I GBRBMTNGQBKBQE-UHFFFAOYSA-L 0.000 description 2
230000008878 coupling Effects 0.000 description 2
238000010168 coupling process Methods 0.000 description 2
125000000000 cycloalkoxy group Chemical group 0.000 description 2
OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 2
206010012601 diabetes mellitus Diseases 0.000 description 2
239000000539 dimer Substances 0.000 description 2
PZPGRFITIJYNEJ-UHFFFAOYSA-N disilane Chemical compound [SiH3][SiH3] PZPGRFITIJYNEJ-UHFFFAOYSA-N 0.000 description 2
229940079593 drug Drugs 0.000 description 2
239000003480 eluent Substances 0.000 description 2
150000002148 esters Chemical class 0.000 description 2
QQXQAEWRSVZPJM-UHFFFAOYSA-N ethyl 1h-indole-2-carboxylate Chemical compound C1=CC=C2NC(C(=O)OCC)=CC2=C1 QQXQAEWRSVZPJM-UHFFFAOYSA-N 0.000 description 2
HVJJYOAPXBPQQV-UHFFFAOYSA-N ethyl 2-azidoacetate Chemical compound CCOC(=O)CN=[N+]=[N-] HVJJYOAPXBPQQV-UHFFFAOYSA-N 0.000 description 2
CFJMUFODYJVMCX-UHFFFAOYSA-N ethyl 6-trimethylsilyl-1h-indole-2-carboxylate Chemical compound C1=C([Si](C)(C)C)C=C2NC(C(=O)OCC)=CC2=C1 CFJMUFODYJVMCX-UHFFFAOYSA-N 0.000 description 2
125000004428 fluoroalkoxy group Chemical group 0.000 description 2
125000005553 heteroaryloxy group Chemical group 0.000 description 2
NEXSMEBSBIABKL-UHFFFAOYSA-N hexamethyldisilane Chemical compound C[Si](C)(C)[Si](C)(C)C NEXSMEBSBIABKL-UHFFFAOYSA-N 0.000 description 2
150000004677 hydrates Chemical class 0.000 description 2
125000002768 hydroxyalkyl group Chemical group 0.000 description 2
238000002347 injection Methods 0.000 description 2
239000007924 injection Substances 0.000 description 2
PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 2
229910052740 iodine Inorganic materials 0.000 description 2
239000011630 iodine Substances 0.000 description 2
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
229940126601 medicinal product Drugs 0.000 description 2
230000002503 metabolic effect Effects 0.000 description 2
125000002950 monocyclic group Chemical group 0.000 description 2
125000003431 oxalo group Chemical group 0.000 description 2
229910052760 oxygen Inorganic materials 0.000 description 2
239000001301 oxygen Substances 0.000 description 2
NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 2
SIOXPEMLGUPBBT-UHFFFAOYSA-N picolinic acid Chemical compound OC(=O)C1=CC=CC=N1 SIOXPEMLGUPBBT-UHFFFAOYSA-N 0.000 description 2
125000006239 protecting group Chemical group 0.000 description 2
PTMBWNZJOQBTBK-UHFFFAOYSA-N pyridin-4-ylmethanol Chemical compound OCC1=CC=NC=C1 PTMBWNZJOQBTBK-UHFFFAOYSA-N 0.000 description 2
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
102000005962 receptors Human genes 0.000 description 2
108020003175 receptors Proteins 0.000 description 2
239000010948 rhodium Substances 0.000 description 2
238000007665 sagging Methods 0.000 description 2
238000010898 silica gel chromatography Methods 0.000 description 2
239000012312 sodium hydride Substances 0.000 description 2
229910000104 sodium hydride Inorganic materials 0.000 description 2
125000000446 sulfanediyl group Chemical group *S* 0.000 description 2
239000011593 sulfur Substances 0.000 description 2
239000003826 tablet Substances 0.000 description 2
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
125000004001 thioalkyl group Chemical group 0.000 description 2
SSJXIUAHEKJCMH-PHDIDXHHSA-N (1r,2r)-cyclohexane-1,2-diamine Chemical compound N[C@@H]1CCCC[C@H]1N SSJXIUAHEKJCMH-PHDIDXHHSA-N 0.000 description 1
125000004178 (C1-C4) alkyl group Chemical group 0.000 description 1
WAPNOHKVXSQRPX-SSDOTTSWSA-N (R)-1-phenylethanol Chemical compound C[C@@H](O)C1=CC=CC=C1 WAPNOHKVXSQRPX-SSDOTTSWSA-N 0.000 description 1
JSRLURSZEMLAFO-UHFFFAOYSA-N 1,3-dibromobenzene Chemical compound BrC1=CC=CC(Br)=C1 JSRLURSZEMLAFO-UHFFFAOYSA-N 0.000 description 1
JNHDLNXNYPLBMJ-UHFFFAOYSA-N 1,3-thiazol-2-ylmethanol Chemical compound OCC1=NC=CS1 JNHDLNXNYPLBMJ-UHFFFAOYSA-N 0.000 description 1
FQUYSHZXSKYCSY-UHFFFAOYSA-N 1,4-diazepane Chemical compound C1CNCCNC1 FQUYSHZXSKYCSY-UHFFFAOYSA-N 0.000 description 1
QXPLMRNFQQYFBO-UHFFFAOYSA-N 1-(1,3-thiazol-2-ylmethyl)-5-trimethylsilylindole-2-carboxylic acid Chemical compound OC(=O)C1=CC2=CC([Si](C)(C)C)=CC=C2N1CC1=NC=CS1 QXPLMRNFQQYFBO-UHFFFAOYSA-N 0.000 description 1
AUKFDIFLZGXBKD-UHFFFAOYSA-N 1-(pyridin-4-ylmethyl)pyrrolo[2,3-b]pyridine-2-carboxamide Chemical compound N1=CC=C(C=C1)CN1C(=CC=2C1=NC=CC=2)C(=O)N AUKFDIFLZGXBKD-UHFFFAOYSA-N 0.000 description 1
ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 1
ZPYIGTSNTOLSHW-UHFFFAOYSA-N 1-[(3-methylphenyl)methyl]-6-trimethylsilylindole-2-carboxylic acid Chemical compound CC1=CC=CC(CN2C3=CC(=CC=C3C=C2C(O)=O)[Si](C)(C)C)=C1 ZPYIGTSNTOLSHW-UHFFFAOYSA-N 0.000 description 1
JRHPOFJADXHYBR-UHFFFAOYSA-N 1-n,2-n-dimethylcyclohexane-1,2-diamine Chemical compound CNC1CCCCC1NC JRHPOFJADXHYBR-UHFFFAOYSA-N 0.000 description 1
SODQFLRLAOALCF-UHFFFAOYSA-N 1lambda3-bromacyclohexa-1,3,5-triene Chemical compound Br1=CC=CC=C1 SODQFLRLAOALCF-UHFFFAOYSA-N 0.000 description 1
VNOMEAQPOMDWSR-UHFFFAOYSA-N 2,2,2-trifluoro-1-phenylethanol Chemical compound FC(F)(F)C(O)C1=CC=CC=C1 VNOMEAQPOMDWSR-UHFFFAOYSA-N 0.000 description 1
FJRPOHLDJUJARI-UHFFFAOYSA-N 2,3-dihydro-1,2-oxazole Chemical compound C1NOC=C1 FJRPOHLDJUJARI-UHFFFAOYSA-N 0.000 description 1
ZABMHLDQFJHDSC-UHFFFAOYSA-N 2,3-dihydro-1,3-oxazole Chemical compound C1NC=CO1 ZABMHLDQFJHDSC-UHFFFAOYSA-N 0.000 description 1
GKPKTWSOYNGGKV-UHFFFAOYSA-N 2,3-dimethylimidazo[4,5-b]pyridin-6-amine;hydrochloride Chemical compound Cl.NC1=CN=C2N(C)C(C)=NC2=C1 GKPKTWSOYNGGKV-UHFFFAOYSA-N 0.000 description 1
QLHVJBXAQWPEDI-UHFFFAOYSA-N 2-chloro-3,5-dinitropyridine Chemical compound [O-][N+](=O)C1=CN=C(Cl)C([N+]([O-])=O)=C1 QLHVJBXAQWPEDI-UHFFFAOYSA-N 0.000 description 1
CWHQZQFLWREZTA-UHFFFAOYSA-N 2-methyl-6-nitro-1h-imidazo[4,5-b]pyridine Chemical compound [O-][N+](=O)C1=CN=C2NC(C)=NC2=C1 CWHQZQFLWREZTA-UHFFFAOYSA-N 0.000 description 1
ZWVNGEFNOFLAGN-UHFFFAOYSA-N 2-methyl-[1,3]thiazolo[5,4-b]pyridin-6-amine Chemical compound NC1=CN=C2SC(C)=NC2=C1 ZWVNGEFNOFLAGN-UHFFFAOYSA-N 0.000 description 1
SKMJUJOLGJLTOJ-UHFFFAOYSA-N 2-n-methyl-5-nitropyridine-2,3-diamine Chemical compound CNC1=NC=C([N+]([O-])=O)C=C1N SKMJUJOLGJLTOJ-UHFFFAOYSA-N 0.000 description 1
FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 1
SVNCRRZKBNSMIV-UHFFFAOYSA-N 3-Aminoquinoline Chemical compound C1=CC=CC2=CC(N)=CN=C21 SVNCRRZKBNSMIV-UHFFFAOYSA-N 0.000 description 1
BXNPMKKQEZAHDO-UHFFFAOYSA-N 3-amino-5,6,7,8-tetrahydroquinolin-6-ol Chemical compound C1CC(O)CC2=CC(N)=CN=C21 BXNPMKKQEZAHDO-UHFFFAOYSA-N 0.000 description 1
KMNNVCWSIWTUSL-UHFFFAOYSA-N 3-methylimidazo[4,5-b]pyridin-6-amine Chemical compound NC1=CN=C2N(C)C=NC2=C1 KMNNVCWSIWTUSL-UHFFFAOYSA-N 0.000 description 1
OXWTXKZCMKXEBO-UHFFFAOYSA-N 4-methyl-2,3-dihydropyrido[3,2-b][1,4]oxazin-7-amine Chemical compound NC1=CN=C2N(C)CCOC2=C1 OXWTXKZCMKXEBO-UHFFFAOYSA-N 0.000 description 1
BPCNVZGALJUWSO-UHFFFAOYSA-N 4-trimethylsilylbenzaldehyde Chemical compound C[Si](C)(C)C1=CC=C(C=O)C=C1 BPCNVZGALJUWSO-UHFFFAOYSA-N 0.000 description 1
JOQJNCSAEMIZOU-UHFFFAOYSA-N 5-nitropyridine-2,3-diamine Chemical compound NC1=CC([N+]([O-])=O)=CN=C1N JOQJNCSAEMIZOU-UHFFFAOYSA-N 0.000 description 1
XYQGZTAAYQGHCB-UHFFFAOYSA-N 6-trimethylsilyl-1H-indole-2-carboxylic acid Chemical compound C[Si](C)(C)C1=CC=C2C=C(C(O)=O)NC2=C1 XYQGZTAAYQGHCB-UHFFFAOYSA-N 0.000 description 1
UTPFXZJAASMEDW-UHFFFAOYSA-N 7-bromo-1h-pyrido[2,3-b][1,4]oxazin-2-one Chemical compound O1CC(=O)NC2=CC(Br)=CN=C21 UTPFXZJAASMEDW-UHFFFAOYSA-N 0.000 description 1
PMNCDNRJLYPTDB-UHFFFAOYSA-N 7-bromo-2,3-dihydro-[1,4]dioxino[2,3-b]pyridine Chemical compound O1CCOC2=CC(Br)=CN=C21 PMNCDNRJLYPTDB-UHFFFAOYSA-N 0.000 description 1
CYISPVTTZWJFEO-UHFFFAOYSA-N 7-bromo-3,4-dihydro-2h-pyrido[3,2-b][1,4]oxazine Chemical compound N1CCOC2=CC(Br)=CN=C21 CYISPVTTZWJFEO-UHFFFAOYSA-N 0.000 description 1
208000004998 Abdominal Pain Diseases 0.000 description 1
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
208000008035 Back Pain Diseases 0.000 description 1
BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
108091003079 Bovine Serum Albumin Proteins 0.000 description 1
206010006482 Bronchospasm Diseases 0.000 description 1
SAMYHDFKQQRAQE-UHFFFAOYSA-N CI.BrC1=CC2=C(OCC(N2C)=O)N=C1 Chemical compound CI.BrC1=CC2=C(OCC(N2C)=O)N=C1 SAMYHDFKQQRAQE-UHFFFAOYSA-N 0.000 description 1
BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 1
208000002881 Colic Diseases 0.000 description 1
229920002261 Corn starch Polymers 0.000 description 1
206010011224 Cough Diseases 0.000 description 1
FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 1
206010013935 Dysmenorrhoea Diseases 0.000 description 1
208000001375 Facial Neuralgia Diseases 0.000 description 1
208000001640 Fibromyalgia Diseases 0.000 description 1
CEAZRRDELHUEMR-URQXQFDESA-N Gentamicin Chemical compound O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N CEAZRRDELHUEMR-URQXQFDESA-N 0.000 description 1
229930182566 Gentamicin Natural products 0.000 description 1
206010019233 Headaches Diseases 0.000 description 1
206010020751 Hypersensitivity Diseases 0.000 description 1
206010020853 Hypertonic bladder Diseases 0.000 description 1
206010021639 Incontinence Diseases 0.000 description 1
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
229930195725 Mannitol Natural products 0.000 description 1
AFVFQIVMOAPDHO-UHFFFAOYSA-M Methanesulfonate Chemical compound CS([O-])(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 1
208000019695 Migraine disease Diseases 0.000 description 1
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical group C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 1
208000000112 Myalgia Diseases 0.000 description 1
HSHXDCVZWHOWCS-UHFFFAOYSA-N N'-hexadecylthiophene-2-carbohydrazide Chemical compound CCCCCCCCCCCCCCCCNNC(=O)c1cccs1 HSHXDCVZWHOWCS-UHFFFAOYSA-N 0.000 description 1
150000001204 N-oxides Chemical class 0.000 description 1
238000005481 NMR spectroscopy Methods 0.000 description 1
239000007832 Na2SO4 Substances 0.000 description 1
206010029174 Nerve compression Diseases 0.000 description 1
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
206010030216 Oesophagitis Diseases 0.000 description 1
206010033645 Pancreatitis Diseases 0.000 description 1
208000000450 Pelvic Pain Diseases 0.000 description 1
208000008469 Peptic Ulcer Diseases 0.000 description 1
239000004698 Polyethylene Substances 0.000 description 1
206010038419 Renal colic Diseases 0.000 description 1
206010038743 Restlessness Diseases 0.000 description 1
208000025747 Rheumatic disease Diseases 0.000 description 1
208000007893 Salpingitis Diseases 0.000 description 1
206010042496 Sunburn Diseases 0.000 description 1
208000030886 Traumatic Brain injury Diseases 0.000 description 1
206010046543 Urinary incontinence Diseases 0.000 description 1
208000003728 Vulvodynia Diseases 0.000 description 1
206010069055 Vulvovaginal pain Diseases 0.000 description 1
XZXNGMQCDZNJPU-UHFFFAOYSA-N [1,3]thiazolo[5,4-b]pyridin-6-amine Chemical compound NC1=CN=C2SC=NC2=C1 XZXNGMQCDZNJPU-UHFFFAOYSA-N 0.000 description 1
BXEHKCUWIODEDE-UHFFFAOYSA-N [3-(trifluoromethyl)phenyl]methanol Chemical compound OCC1=CC=CC(C(F)(F)F)=C1 BXEHKCUWIODEDE-UHFFFAOYSA-N 0.000 description 1
DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 1
230000004913 activation Effects 0.000 description 1
239000013543 active substance Substances 0.000 description 1
230000010933 acylation Effects 0.000 description 1
238000005917 acylation reaction Methods 0.000 description 1
239000000654 additive Substances 0.000 description 1
230000000996 additive effect Effects 0.000 description 1
230000001476 alcoholic effect Effects 0.000 description 1
125000001931 aliphatic group Chemical group 0.000 description 1
150000004791 alkyl magnesium halides Chemical class 0.000 description 1
125000004414 alkyl thio group Chemical group 0.000 description 1
208000026935 allergic disease Diseases 0.000 description 1
229910052782 aluminium Inorganic materials 0.000 description 1
229910021529 ammonia Inorganic materials 0.000 description 1
150000008064 anhydrides Chemical class 0.000 description 1
230000003217 anti-cancerogenic effect Effects 0.000 description 1
229940053202 antiepileptics carboxamide derivative Drugs 0.000 description 1
239000011260 aqueous acid Substances 0.000 description 1
230000002917 arthritic effect Effects 0.000 description 1
150000001543 aryl boronic acids Chemical class 0.000 description 1
125000005110 aryl thio group Chemical group 0.000 description 1
208000006673 asthma Diseases 0.000 description 1
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
XYOVOXDWRFGKEX-UHFFFAOYSA-N azepine Chemical compound N1C=CC=CC=C1 XYOVOXDWRFGKEX-UHFFFAOYSA-N 0.000 description 1
125000002785 azepinyl group Chemical group 0.000 description 1
HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 description 1
125000002393 azetidinyl group Chemical group 0.000 description 1
230000003542 behavioural effect Effects 0.000 description 1
SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
229940077388 benzenesulfonate Drugs 0.000 description 1
125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
230000037396 body weight Effects 0.000 description 1
238000009835 boiling Methods 0.000 description 1
239000012267 brine Substances 0.000 description 1
230000007885 bronchoconstriction Effects 0.000 description 1
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
201000011510 cancer Diseases 0.000 description 1
BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical class OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
239000003054 catalyst Substances 0.000 description 1
125000002091 cationic group Chemical group 0.000 description 1
210000003169 central nervous system Anatomy 0.000 description 1
239000003638 chemical reducing agent Substances 0.000 description 1
230000001684 chronic effect Effects 0.000 description 1
229940114081 cinnamate Drugs 0.000 description 1
125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 description 1
206010009887 colitis Diseases 0.000 description 1
239000012141 concentrate Substances 0.000 description 1
150000004696 coordination complex Chemical class 0.000 description 1
239000008120 corn starch Substances 0.000 description 1
208000012790 cranial neuralgia Diseases 0.000 description 1
239000006071 cream Substances 0.000 description 1
238000002425 crystallisation Methods 0.000 description 1
230000008025 crystallization Effects 0.000 description 1
238000012258 culturing Methods 0.000 description 1
125000006165 cyclic alkyl group Chemical group 0.000 description 1
125000001047 cyclobutenyl group Chemical group C1(=CCC1)* 0.000 description 1
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 1
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
125000000298 cyclopropenyl group Chemical group [H]C1=C([H])C1([H])* 0.000 description 1
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
201000003146 cystitis Diseases 0.000 description 1
229940104302 cytosine Drugs 0.000 description 1
238000000354 decomposition reaction Methods 0.000 description 1
238000000586 desensitisation Methods 0.000 description 1
238000010586 diagram Methods 0.000 description 1
150000004985 diamines Chemical class 0.000 description 1
ZWWWLCMDTZFSOO-UHFFFAOYSA-N diethoxyphosphorylformonitrile Chemical compound CCOP(=O)(C#N)OCC ZWWWLCMDTZFSOO-UHFFFAOYSA-N 0.000 description 1
125000005047 dihydroimidazolyl group Chemical group N1(CNC=C1)* 0.000 description 1
125000005050 dihydrooxazolyl group Chemical group O1C(NC=C1)* 0.000 description 1
125000005054 dihydropyrrolyl group Chemical group [H]C1=C([H])C([H])([H])C([H])([H])N1* 0.000 description 1
125000005056 dihydrothiazolyl group Chemical group S1C(NC=C1)* 0.000 description 1
238000002224 dissection Methods 0.000 description 1
208000000718 duodenal ulcer Diseases 0.000 description 1
201000006549 dyspepsia Diseases 0.000 description 1
230000007831 electrophysiology Effects 0.000 description 1
238000002001 electrophysiology Methods 0.000 description 1
208000006881 esophagitis Diseases 0.000 description 1
125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
QBDAQDGVEMZCCF-UHFFFAOYSA-N ethyl 1-(pyridin-4-ylmethyl)-5-trimethylsilylindole-2-carboxylate Chemical compound CCOC(=O)C1=CC2=CC([Si](C)(C)C)=CC=C2N1CC1=CC=NC=C1 QBDAQDGVEMZCCF-UHFFFAOYSA-N 0.000 description 1
BHZZNEHJBQKOKP-UHFFFAOYSA-N ethyl 1-(pyridin-4-ylmethyl)-6-trimethylsilylindole-2-carboxylate Chemical compound CCOC(=O)C1=CC2=CC=C([Si](C)(C)C)C=C2N1CC1=CC=NC=C1 BHZZNEHJBQKOKP-UHFFFAOYSA-N 0.000 description 1
YJZKBIKUIOCDAN-UHFFFAOYSA-N ethyl 1-[(3-methylphenyl)methyl]-5-(trifluoromethyl)indole-2-carboxylate Chemical compound CCOC(=O)C1=CC2=CC(C(F)(F)F)=CC=C2N1CC1=CC=CC(C)=C1 YJZKBIKUIOCDAN-UHFFFAOYSA-N 0.000 description 1
CBIVEMGUNRNUEB-UHFFFAOYSA-N ethyl 1h-pyrrolo[2,3-b]pyridine-2-carboxylate Chemical compound C1=CN=C2NC(C(=O)OCC)=CC2=C1 CBIVEMGUNRNUEB-UHFFFAOYSA-N 0.000 description 1
PHQNULAMYSYZJY-UHFFFAOYSA-N ethyl 2-azido-3-(3-trimethylsilylphenyl)prop-2-enoate Chemical compound CCOC(=O)C(N=[N+]=[N-])=CC1=CC=CC([Si](C)(C)C)=C1 PHQNULAMYSYZJY-UHFFFAOYSA-N 0.000 description 1
YNSYGBUYCMWPBF-UHFFFAOYSA-N ethyl 2-azido-3-(4-trimethylsilylphenyl)prop-2-enoate Chemical compound CCOC(=O)C(N=[N+]=[N-])=CC1=CC=C([Si](C)(C)C)C=C1 YNSYGBUYCMWPBF-UHFFFAOYSA-N 0.000 description 1
239000012894 fetal calf serum Substances 0.000 description 1
125000003709 fluoroalkyl group Chemical group 0.000 description 1
125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
239000012458 free base Substances 0.000 description 1
230000005714 functional activity Effects 0.000 description 1
210000000609 ganglia Anatomy 0.000 description 1
229960002518 gentamicin Drugs 0.000 description 1
ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
239000008187 granular material Substances 0.000 description 1
230000005484 gravity Effects 0.000 description 1
150000004820 halides Chemical class 0.000 description 1
239000007902 hard capsule Substances 0.000 description 1
231100000869 headache Toxicity 0.000 description 1
238000010438 heat treatment Methods 0.000 description 1
230000002008 hemorrhagic effect Effects 0.000 description 1
230000002440 hepatic effect Effects 0.000 description 1
125000005368 heteroarylthio group Chemical group 0.000 description 1
239000012456 homogeneous solution Substances 0.000 description 1
150000004678 hydrides Chemical class 0.000 description 1
NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
208000013403 hyperactivity Diseases 0.000 description 1
230000009610 hypersensitivity Effects 0.000 description 1
230000000642 iatrogenic effect Effects 0.000 description 1
239000005457 ice water Substances 0.000 description 1
239000007943 implant Substances 0.000 description 1
125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
125000001041 indolyl group Chemical group 0.000 description 1
208000015181 infectious disease Diseases 0.000 description 1
230000002458 infectious effect Effects 0.000 description 1
230000002757 inflammatory effect Effects 0.000 description 1
238000002329 infrared spectrum Methods 0.000 description 1
239000000543 intermediate Substances 0.000 description 1
208000028774 intestinal disease Diseases 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
229910052742 iron Inorganic materials 0.000 description 1
208000002551 irritable bowel syndrome Diseases 0.000 description 1
208000028867 ischemia Diseases 0.000 description 1
125000001977 isobenzofuranyl group Chemical group C=1(OC=C2C=CC=CC12)* 0.000 description 1
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
KQNPFQTWMSNSAP-UHFFFAOYSA-M isobutyrate Chemical compound CC(C)C([O-])=O KQNPFQTWMSNSAP-UHFFFAOYSA-M 0.000 description 1
125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
238000002955 isolation Methods 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 1
150000003951 lactams Chemical class 0.000 description 1
CFHGBZLNZZVTAY-UHFFFAOYSA-N lawesson's reagent Chemical compound C1=CC(OC)=CC=C1P1(=S)SP(=S)(C=2C=CC(OC)=CC=2)S1 CFHGBZLNZZVTAY-UHFFFAOYSA-N 0.000 description 1
238000004811 liquid chromatography Methods 0.000 description 1
229910052744 lithium Inorganic materials 0.000 description 1
239000006210 lotion Substances 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
RDPLOLUNEKBWBR-UHFFFAOYSA-L magnesium;sodium;sulfate Chemical compound [Na+].[Mg+2].[O-]S([O-])(=O)=O RDPLOLUNEKBWBR-UHFFFAOYSA-L 0.000 description 1
206010025482 malaise Diseases 0.000 description 1
239000000594 mannitol Substances 0.000 description 1
235000010355 mannitol Nutrition 0.000 description 1
238000004949 mass spectrometry Methods 0.000 description 1
238000002844 melting Methods 0.000 description 1
230000008018 melting Effects 0.000 description 1
210000004379 membrane Anatomy 0.000 description 1
239000012528 membrane Substances 0.000 description 1
VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 1
NBTOZLQBSIZIKS-UHFFFAOYSA-N methoxide Chemical compound [O-]C NBTOZLQBSIZIKS-UHFFFAOYSA-N 0.000 description 1
230000027939 micturition Effects 0.000 description 1
206010027599 migraine Diseases 0.000 description 1
125000002757 morpholinyl group Chemical group 0.000 description 1
208000013465 muscle pain Diseases 0.000 description 1
WSMCKWSNTUIJHW-UHFFFAOYSA-N n-[2-(hydroxymethyl)-[1,3]thiazolo[5,4-b]pyridin-6-yl]-1-(1,3-thiazol-2-ylmethyl)-6-trimethylsilylindole-2-carboxamide Chemical compound C12=CC([Si](C)(C)C)=CC=C2C=C(C(=O)NC=2C=C3N=C(CO)SC3=NC=2)N1CC1=NC=CS1 WSMCKWSNTUIJHW-UHFFFAOYSA-N 0.000 description 1
125000001624 naphthyl group Chemical group 0.000 description 1
230000001537 neural effect Effects 0.000 description 1
208000004296 neuralgia Diseases 0.000 description 1
230000004770 neurodegeneration Effects 0.000 description 1
210000002569 neuron Anatomy 0.000 description 1
230000002981 neuropathic effect Effects 0.000 description 1
238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
239000002674 ointment Substances 0.000 description 1
230000003647 oxidation Effects 0.000 description 1
238000007254 oxidation reaction Methods 0.000 description 1
125000004043 oxo group Chemical group O=* 0.000 description 1
238000012402 patch clamp technique Methods 0.000 description 1
239000008188 pellet Substances 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
208000011906 peptic ulcer disease Diseases 0.000 description 1
230000002093 peripheral effect Effects 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
239000012071 phase Substances 0.000 description 1
XYFCBTPGUUZFHI-UHFFFAOYSA-O phosphonium Chemical compound [PH4+] XYFCBTPGUUZFHI-UHFFFAOYSA-O 0.000 description 1
125000004193 piperazinyl group Chemical group 0.000 description 1
125000003386 piperidinyl group Chemical group 0.000 description 1
IUGYQRQAERSCNH-UHFFFAOYSA-M pivalate Chemical compound CC(C)(C)C([O-])=O IUGYQRQAERSCNH-UHFFFAOYSA-M 0.000 description 1
229950010765 pivalate Drugs 0.000 description 1
229920000573 polyethylene Polymers 0.000 description 1
BDAWXSQJJCIFIK-UHFFFAOYSA-N potassium methoxide Chemical compound [K+].[O-]C BDAWXSQJJCIFIK-UHFFFAOYSA-N 0.000 description 1
JSEOZCYBUXHPEA-UHFFFAOYSA-N propanoic acid 5-(trifluoromethyl)-1H-indole Chemical compound CCC(=O)O.FC(C=1C=C2C=CNC2=CC1)(F)F JSEOZCYBUXHPEA-UHFFFAOYSA-N 0.000 description 1
AWHVLNQSKYBGAP-UHFFFAOYSA-N propanoic acid;5-(trifluoromethyl)-1h-pyrrolo[2,3-b]pyridine Chemical compound CCC(O)=O.FC(F)(F)C1=CN=C2NC=CC2=C1 AWHVLNQSKYBGAP-UHFFFAOYSA-N 0.000 description 1
238000011321 prophylaxis Methods 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
230000001012 protector Effects 0.000 description 1
125000002112 pyrrolidino group Chemical group [*]N1C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
239000012429 reaction media Substances 0.000 description 1
230000009467 reduction Effects 0.000 description 1
230000011514 reflex Effects 0.000 description 1
208000023504 respiratory system disease Diseases 0.000 description 1
230000000552 rheumatic effect Effects 0.000 description 1
229910052703 rhodium Inorganic materials 0.000 description 1
MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
238000005070 sampling Methods 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
239000012279 sodium borohydride Substances 0.000 description 1
229910000033 sodium borohydride Inorganic materials 0.000 description 1
CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
239000007901 soft capsule Substances 0.000 description 1
230000006641 stabilisation Effects 0.000 description 1
238000011105 stabilization Methods 0.000 description 1
239000007858 starting material Substances 0.000 description 1
210000002784 stomach Anatomy 0.000 description 1
238000006467 substitution reaction Methods 0.000 description 1
HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 description 1
229940124530 sulfonamide Drugs 0.000 description 1
150000003456 sulfonamides Chemical class 0.000 description 1
230000006103 sulfonylation Effects 0.000 description 1
238000005694 sulfonylation reaction Methods 0.000 description 1
125000004853 tetrahydropyridinyl group Chemical group N1(CCCC=C1)* 0.000 description 1
BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
125000004568 thiomorpholinyl group Chemical group 0.000 description 1
HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 description 1
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
230000000699 topical effect Effects 0.000 description 1
231100000331 toxic Toxicity 0.000 description 1
230000002588 toxic effect Effects 0.000 description 1
230000000472 traumatic effect Effects 0.000 description 1
ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
125000002827 triflate group Chemical group FC(S(=O)(=O)O*)(F)F 0.000 description 1
KXFSUVJPEQYUGN-UHFFFAOYSA-N trimethyl(phenyl)silane Chemical compound C[Si](C)(C)C1=CC=CC=C1 KXFSUVJPEQYUGN-UHFFFAOYSA-N 0.000 description 1
LEIMLDGFXIOXMT-UHFFFAOYSA-N trimethylsilyl cyanide Chemical compound C[Si](C)(C)C#N LEIMLDGFXIOXMT-UHFFFAOYSA-N 0.000 description 1
239000001226 triphosphate Substances 0.000 description 1
235000011178 triphosphate Nutrition 0.000 description 1
UNXRWKVEANCORM-UHFFFAOYSA-N triphosphoric acid Chemical compound OP(O)(=O)OP(O)(=O)OP(O)(O)=O UNXRWKVEANCORM-UHFFFAOYSA-N 0.000 description 1
238000001665 trituration Methods 0.000 description 1
208000014001 urinary system disease Diseases 0.000 description 1
239000008096 xylene Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/04—Antipruritics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/14—Decongestants or antiallergics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/20—Antivirals for DNA viruses
- A61P31/22—Antivirals for DNA viruses for herpes viruses
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D513/04—Ortho-condensed systems

Landscapes

Health & Medical Sciences (AREA)
Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Pharmacology & Pharmacy (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Virology (AREA)
Dermatology (AREA)
Pain & Pain Management (AREA)
Ophthalmology & Optometry (AREA)
Oncology (AREA)
Urology & Nephrology (AREA)
Communicable Diseases (AREA)
Biomedical Technology (AREA)
Neurology (AREA)
Neurosurgery (AREA)
Hematology (AREA)
Endocrinology (AREA)
Diabetes (AREA)
Psychiatry (AREA)
Obesity (AREA)
Molecular Biology (AREA)
Biotechnology (AREA)
Rheumatology (AREA)
Reproductive Health (AREA)
Pulmonology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Plural Heterocyclic Compounds (AREA)
Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)

CA2712914A 2008-01-22 2009-01-20 Derives bicycliques de carboxamides azabicycliques, leur preparation et leur application en therapeutique Expired - Fee Related CA2712914C (fr)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
FR0800309		2008-01-22
FR0800309A FR2926555B1 (fr)	2008-01-22	2008-01-22	Derives bicycliques de carboxamides azabicycliques, leur preparation et leur application en therapeutique
PCT/FR2009/000051 WO2009112677A2 (fr)	2008-01-22	2009-01-20	Dérivés bicycliques de carboxamides azabicycliques, leur préparation et leur application en thérapeutique.

Publications (2)

Publication Number	Publication Date
CA2712914A1 CA2712914A1 (fr)	2009-09-17
CA2712914C true CA2712914C (fr)	2016-08-16

Family

ID=39832022

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA2712914A Expired - Fee Related CA2712914C (fr)	2008-01-22	2009-01-20	Derives bicycliques de carboxamides azabicycliques, leur preparation et leur application en therapeutique

Country Status (28)

Country	Link
US (2)	US8299114B2 (es)
EP (1)	EP2235014B1 (es)
JP (1)	JP5457370B2 (es)
KR (1)	KR20100110876A (es)
CN (1)	CN101959877A (es)
AR (1)	AR070207A1 (es)
AU (1)	AU2009224532B2 (es)
BR (1)	BRPI0907628A2 (es)
CA (1)	CA2712914C (es)
CO (1)	CO6220953A2 (es)
CR (1)	CR11574A (es)
DO (1)	DOP2010000227A (es)
EA (1)	EA201070871A1 (es)
EC (1)	ECSP10010359A (es)
FR (1)	FR2926555B1 (es)
HN (1)	HN2010001460A (es)
IL (1)	IL207084A0 (es)
MA (1)	MA32088B1 (es)
MX (1)	MX2010008042A (es)
NI (1)	NI201000123A (es)
NZ (1)	NZ586937A (es)
PA (1)	PA8813101A1 (es)
PE (1)	PE20091321A1 (es)
TW (1)	TWI394743B (es)
UA (1)	UA102679C2 (es)
UY (1)	UY31607A1 (es)
WO (1)	WO2009112677A2 (es)
ZA (1)	ZA201005205B (es)

Families Citing this family (25)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
FR2926554B1 (fr) *	2008-01-22	2010-03-12	Sanofi Aventis	Derives de carboxamides azabicycliques, leur preparation et leur application en therapeutique
ES2797123T3 (es)	2011-12-21	2020-12-01	Novira Therapeutics Inc	Agentes antivirales para la hepatitis B
CN104902885A (zh)	2012-08-28	2015-09-09	爱尔兰詹森科学公司	氨磺酰基-芳基酰胺和其作为药物用于治疗乙型肝炎的用途
PL2961732T3 (pl)	2013-02-28	2017-09-29	Janssen Sciences Ireland Uc	Sulfamoilo-aryloamidy i ich stosowanie jako leków do leczenia wirusowego zapalenia wątroby typu B
EA027068B1 (ru)	2013-04-03	2017-06-30	Янссен Сайенсиз Айрлэнд Юси	Производные n-фенилкарбоксамида и их применение в качестве лекарственных препаратов для лечения гепатита b
CN105960400B (zh)	2013-05-17	2019-05-31	爱尔兰詹森科学公司	氨磺酰基噻吩酰胺衍生物及其作为药物用于治疗乙型肝炎的用途
JO3603B1 (ar)	2013-05-17	2020-07-05	Janssen Sciences Ireland Uc	مشتقات سلفامويل بيرولاميد واستخدامها كادوية لمعالجة التهاب الكبد نوع بي
EP3357906B1 (en)	2013-07-25	2019-12-04	Janssen Sciences Ireland Unlimited Company	Glyoxamide substituted pyrrolamide derivatives and the use thereof as medicaments for the treatment of hepatitis b
JP6452119B2 (ja)	2013-10-23	2019-01-16	ヤンセン・サイエンシズ・アイルランド・アンリミテッド・カンパニー	カルボキサミド誘導体およびｂ型肝炎の処置のための医薬品としてのその使用
US9169212B2 (en)	2014-01-16	2015-10-27	Novira Therapeutics, Inc.	Azepane derivatives and methods of treating hepatitis B infections
US10392349B2 (en)	2014-01-16	2019-08-27	Novira Therapeutics, Inc.	Azepane derivatives and methods of treating hepatitis B infections
US20150216938A1 (en)	2014-02-05	2015-08-06	Novira Therapeutics Inc.	Combination therapy for treatment of hbv infections
HK1225389A1 (zh)	2014-02-06	2017-09-08	Janssen Sciences Ireland Uc	氨磺酰基吡咯酰胺衍生物及其作为药物用於治疗乙型肝炎的用途
CA2980298A1 (en)	2015-03-19	2016-09-22	Novira Therapeutics, Inc.	Azocane and azonane derivatives and methods of treating hepatitis b infections
US10875876B2 (en)	2015-07-02	2020-12-29	Janssen Sciences Ireland Uc	Cyclized sulfamoylarylamide derivatives and the use thereof as medicaments for the treatment of hepatitis B
EP3356328A1 (en)	2015-09-29	2018-08-08	Novira Therapeutics, Inc.	Crystalline forms of a hepatitis b antiviral agent
KR20180129943A (ko)	2016-04-15	2018-12-05	노비라 테라퓨틱스, 인코포레이티드	캡시드 조립 억제제를 포함하는 배합물 및 방법
US11014927B2 (en)	2017-03-20	2021-05-25	Forma Therapeutics, Inc.	Pyrrolopyrrole compositions as pyruvate kinase (PKR) activators
MA52019A (fr)	2018-03-14	2021-01-20	Janssen Sciences Ireland Unlimited Co	Schéma posologique de modulateur d'assemblage de capside
MA53668B1 (fr)	2018-09-19	2024-06-28	Novo Nordisk Health Care Ag	Traitement de la drépanocytose avec un composé activant la pyruvate kinase r
JP7450610B2 (ja)	2018-09-19	2024-03-15	ノヴォ・ノルディスク・ヘルス・ケア・アーゲー	ピルビン酸キナーゼｒの活性化
MX2021010145A (es)	2019-02-22	2021-09-14	Janssen Sciences Ireland Unlimited Co	Derivados de amida utiles en el tratamiento de una infeccion por vhb o de enfermedades inducidas por vhb.
EP3966205A1 (en)	2019-05-06	2022-03-16	Janssen Sciences Ireland Unlimited Company	Amide derivatives useful in the treatment of hbv infection or hbv-induced diseases
MA57202B1 (fr)	2019-09-19	2025-09-30	Novo Nordisk Health Care Ag	Compositions d'activation de la pyruvate kinase r (pkr)
US12128035B2 (en)	2021-03-19	2024-10-29	Novo Nordisk Health Care Ag	Activating pyruvate kinase R

Family Cites Families (11)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
JP4413696B2 (ja) *	2004-07-08	2010-02-10	シーケーディ株式会社	薬液供給ユニット
FR2874015B1 (fr) *	2004-08-05	2006-09-15	Sanofi Synthelabo	Derives de n-(1h-indolyl)-1h-indole-2-carboxamides, leur preparation et leur application en therapeutique
JP2006072736A (ja) *	2004-09-02	2006-03-16	Canon Inc	情報処理装置及び方法及びプログラム及び記憶媒体
WO2006072735A1 (fr)	2005-01-05	2006-07-13	Palga International	Procede et installation de fabrication d'un produit alimentaire de forme allongee a l'aide d'un dispositif de restriction et produit alimentaire obtenu
FR2880625B1 (fr) *	2005-01-07	2007-03-09	Sanofi Aventis Sa	Derives de n-(heteroaryl)-1h-indole-2-carboxamides, leur preparation et leur application en therapeutique
EP1739011B1 (en) *	2005-06-30	2008-05-14	Agusta S.p.A.	Improved helicopter transmission
FR2888848B1 (fr) *	2005-07-22	2007-09-28	Sanofi Aventis Sa	Derives de n-(arylalkyl)-1h-pyrrrolopyridine-2-carboxamides, leur preparation et leur application en therapeutique
FR2888847B1 (fr) *	2005-07-22	2007-08-31	Sanofi Aventis Sa	Derives de n-(heteriaryl)-1-heteorarylalkyl-1h-indole-2- carboxamides, leur preparation et application en therapeutique
FR2897061B1 (fr) *	2006-02-03	2010-09-03	Sanofi Aventis	Derives de n-heteroaryl-carboxamides tricycliques contenant un motif benzimidazole, leur preparation et leur application en therapeutique.
FR2911604B1 (fr) *	2007-01-19	2009-04-17	Sanofi Aventis Sa	Derives de n-(heteroaryl-1h-indole-2-carboxamides, leur preparation et leur application en therapeutique
FR2926554B1 (fr) *	2008-01-22	2010-03-12	Sanofi Aventis	Derives de carboxamides azabicycliques, leur preparation et leur application en therapeutique

2008
- 2008-01-22 FR FR0800309A patent/FR2926555B1/fr not_active Expired - Fee Related
2009
- 2009-01-20 NZ NZ586937A patent/NZ586937A/en not_active IP Right Cessation
- 2009-01-20 PE PE2009000065A patent/PE20091321A1/es not_active Application Discontinuation
- 2009-01-20 CA CA2712914A patent/CA2712914C/fr not_active Expired - Fee Related
- 2009-01-20 WO PCT/FR2009/000051 patent/WO2009112677A2/fr not_active Ceased
- 2009-01-20 JP JP2010543538A patent/JP5457370B2/ja not_active Expired - Fee Related
- 2009-01-20 KR KR1020107018567A patent/KR20100110876A/ko not_active Withdrawn
- 2009-01-20 AR ARP090100167A patent/AR070207A1/es not_active Application Discontinuation
- 2009-01-20 UA UAA201010235A patent/UA102679C2/ru unknown
- 2009-01-20 EP EP09718719.9A patent/EP2235014B1/fr active Active
- 2009-01-20 BR BRPI0907628-0A patent/BRPI0907628A2/pt not_active IP Right Cessation
- 2009-01-20 MX MX2010008042A patent/MX2010008042A/es active IP Right Grant
- 2009-01-20 CN CN2009801063039A patent/CN101959877A/zh active Pending
- 2009-01-20 AU AU2009224532A patent/AU2009224532B2/en not_active Ceased
- 2009-01-20 EA EA201070871A patent/EA201070871A1/ru unknown
- 2009-01-21 PA PA20098813101A patent/PA8813101A1/es unknown
- 2009-01-21 TW TW098102300A patent/TWI394743B/zh not_active IP Right Cessation
- 2009-01-22 UY UY031607A patent/UY31607A1/es not_active Application Discontinuation
2010
- 2010-07-19 IL IL207084A patent/IL207084A0/en unknown
- 2010-07-20 CR CR11574A patent/CR11574A/es not_active Application Discontinuation
- 2010-07-20 EC EC2010010359A patent/ECSP10010359A/es unknown
- 2010-07-21 ZA ZA2010/05205A patent/ZA201005205B/en unknown
- 2010-07-21 NI NI201000123A patent/NI201000123A/es unknown
- 2010-07-21 HN HN2010001460A patent/HN2010001460A/es unknown
- 2010-07-21 US US12/840,661 patent/US8299114B2/en not_active Expired - Fee Related
- 2010-07-22 DO DO2010000227A patent/DOP2010000227A/es unknown
- 2010-07-22 CO CO10089474A patent/CO6220953A2/es not_active Application Discontinuation
- 2010-08-17 MA MA33096A patent/MA32088B1/fr unknown
2012
- 2012-05-08 US US13/466,629 patent/US8604050B2/en not_active Expired - Fee Related

Also Published As

Publication number	Publication date
CA2712914A1 (fr)	2009-09-17
FR2926555A1 (fr)	2009-07-24
EP2235014B1 (fr)	2013-10-09
NZ586937A (en)	2012-04-27
WO2009112677A3 (fr)	2010-01-21
KR20100110876A (ko)	2010-10-13
JP2011512328A (ja)	2011-04-21
PA8813101A1 (es)	2009-08-26
EA201070871A1 (ru)	2011-02-28
AU2009224532B2 (en)	2013-09-12
HN2010001460A (es)	2013-06-10
CR11574A (es)	2010-10-05
AR070207A1 (es)	2010-03-25
MX2010008042A (es)	2010-08-10
BRPI0907628A2 (pt)	2015-07-21
ZA201005205B (en)	2011-10-26
NI201000123A (es)	2010-12-17
UA102679C2 (ru)	2013-08-12
CN101959877A (zh)	2011-01-26
CO6220953A2 (es)	2010-11-19
US20110009400A1 (en)	2011-01-13
PE20091321A1 (es)	2009-09-21
IL207084A0 (en)	2010-12-30
ECSP10010359A (es)	2010-08-31
WO2009112677A2 (fr)	2009-09-17
DOP2010000227A (es)	2010-08-31
TW200936586A (en)	2009-09-01
TWI394743B (zh)	2013-05-01
JP5457370B2 (ja)	2014-04-02
EP2235014A2 (fr)	2010-10-06
US8299114B2 (en)	2012-10-30
AU2009224532A1 (en)	2009-09-17
FR2926555B1 (fr)	2010-02-19
MA32088B1 (fr)	2011-02-01
UY31607A1 (es)	2009-08-31
US20120252837A1 (en)	2012-10-04
US8604050B2 (en)	2013-12-10

Publication	Publication Date	Title
CA2712914C (fr)	2016-08-16	Derives bicycliques de carboxamides azabicycliques, leur preparation et leur application en therapeutique
CA2712609C (fr)	2016-03-08	Derives de carboxamides azabicycliques, leur preparation et leur application en therapeutique
CA2712921C (fr)	2016-08-02	Derives d'indole 2-carboxamides et d'azaindole 2-carboxamides substitues par un groupe silanyle, leur preparation et leur application en therapeutique
CA2712629C (fr)	2016-08-02	Derives de carboxamides n-azabicycliques, leur preparation et leur application en therapeutique
CA2637333C (fr)	2015-12-29	Derives de n-heteroaryl-carboxamides tricycliques contenant un motif benzimidazole, leur preparation et leur application en therapeutique
WO2008107544A1 (fr)	2008-09-12	Derives de n-(heteroaryl)-1-heteroaryl-1h-indole-2-carboxamides, leur preparation et leur application en therapeutique
CA2615751C (fr)	2013-12-17	Derives de n-(heteroaryl)-1-heteroarylalkyl-1h-indole-2-carboxamides, leur preparation et leur application en therapeutique
CA2615676C (fr)	2013-10-15	Derives de n-(arylalkyl)-1h-pyrrolopyridine-2-carboxamides, leur preparation et leur application en therapeutique
EP2106401B1 (fr)	2012-03-14	Derives de pyrrolopyridine-2-carboxamides, leur preparation et leur application en therapeutique

Legal Events

Date	Code	Title	Description
2013-12-10	EEER	Examination request	Effective date: 20131120
2019-03-04	MKLA	Lapsed	Effective date: 20190121